Bioreactors
OwnerJerry Shevitzinventor
Life of this patent
Estimating the term…
Abstract
Miniature stirred tank bioreactor and system; the bioreactor configured for single use culturing, providing unobstructed culturing volume with sensors, probes and ports using minimally invasive placement in-wall or across the wall methods; the bioreactor further capable of containing scaffolds and features for culturing cells and tissue, including structures providing surfaces for cell growth, and screens for retaining microparticles during media exchange
Claims67
A disposable stir tank bioreactor vessel, said vessel having a working volume of 100 ml or less said vessel comprising a head plate, said head plate comprising an opening through which a gas such as air can be delivered into the interior of the vessel and a drainage tube through which fluid can exit the vessel, said vessel surrounded by a rim to which sensor devices can be added, said vessel further comprising an impeller (stirrer) shaft, said shaft vertically disposed, said vessel being sterile.
A disposable stir tank bioreactor vessel of any one of the foregoing claims, said vessel covered by a removable head plate, which headplate allows full access to the vessel.
A disposable stir tank bioreactor vessel of any one of the foregoing claims, wherein the head plate comprises an opening for an impeller shaft and wherein the shaft is disposed in said opening.
A disposable stir tank bioreactor vessel of any one of the foregoing claims where the head plate contains two sealing rings surrounding the impeller shaft, wherein the rings are separated so that an opening in the shaft between the two rings can connect to a gas source.
A disposable stir tank bioreactor vessel of any of the foregoing claims, said vessel made of plastic (preferably polycarbonate, preferably transparent).
A disposable stir tank bioreactor vessel of any of the foregoing claims, wherein the rim is a “double rim” (one with an outwardly hanging lip) to which sensor devices can be added in the rim space, the rim space being the space under and inside the lip.
A disposable stir tank bioreactor vessel of any of the foregoing claims wherein said rim space comprises rim compartments separated by ribs (or walls).
A disposable stir tank bioreactor system, said system comprising a vessel of any of the foregoing claims, said system with a footprint not exceeding 100 square inches (preferably not exceeding 32 square inches) and a height not exceeding 20 inches (preferably not exceeding 13 inches).
A disposable stir tank bioreactor system comprising a bioreactor controller plus a bioreactor vessel of any of the foregoing claims.
A disposable stir tank bioreactor vessel of any of the foregoing claims wherein inside one or more of said rim compartments there is a sensory device.
A disposable stir tank bioreactor vessel of any of the foregoing claims wherein the sensory device is one that comprises a patch sensor inside the vessel.
A disposable stir tank bioreactor vessel of any of the above claims, wherein the drive shaft extends from above the head plate and, via an opening in the head plate, into the vessel.
A disposable stir tank bioreactor vessel of any one of the above claims wherein the drive shaft comprises one or more impellers anywhere along the shaft, preferably at its lower end.
A disposable stir tank bioreactor system of any one of the above claims wherein the drive shaft comprises holes and accordingly is a sparger that discharges bubbles, the holes/sparger is preferably at the base of the drive shaft.
A disposable stir tank bioreactor system of any one of the above claims wherein the system further comprises a battery or battery pack that is connected to and provides electrical power to the entire system in a manner that the entire system may be relocated while fully operational (preferably to a biological safety hood).
A disposable stir tank bioreactor system of any one of the above claims wherein the system further comprises both a display screen and a central processing unit that connects one or more sensor devices to the display screen and translates the information obtained by the sensor into an image (words, numbers, graphs, etc.) on the screen.
A disposable stir tank bioreactor array, said array comprising a plurality of bioreactor systems of any one of the above claims, in which each vessel is connected via its drainage tube directly to another bioreactor, said connection optionally including the drainage tube of the other bioreactor.
A disposable stir tank bioreactor array of any one of the above claims in which one vessel is a controller bioreactor vessel (a/k/a master bioreactor) and any other vessel is an auxiliary bioreactor vessel, and in which at least one system variable (e.g., pH, dissolved oxygen, or temperature) is directly controlled, in full or in part, only in the controller bioreactor and wherein mixing and exchange of fluid between the controller bioreactor and the other occurs.
A method, said method comprising using any one of the above vessels, systems or arrays in a process for growing biological cells (human cells, animal cells, or microorganisms)
A manifold comprising pump banks, which banks which can interchangeably receive different pumps, valves, and/or switches.
A disposable stir tank bioreactor vessel of any of the above claims, such that the vessel has a working volume in the range 35 ml to 100 ml.
A disposable stir tank bioreactor vessel of any of the above claims, such that the vessel is disposable.
A disposable stir tank bioreactor vessel of any of the above claims wherein the vessel is spherical in a cross-section in a horizontal plane.
A disposable stir tank bioreactor vessel of any of the above claims, wherein the head plate comprises a conduit capable of directing a flow of gases from the periphery of the head plate to the impeller shaft vertically disposed in the head plate.
A disposable stir tank bioreactor vessel of any of the above claims, wherein the compartments in the double rim referred to in a claim comprise a lower wall to form a closed compartment (a/k/a “chamber”).
A disposable stir tank bioreactor vessel of any of the above claims, wherein the double rim referred to in any of the above claims has one or more properties selected from the group consisting of the following:
- it provides a place for attaching sensors located in the air gap to the wall of the vessel, its inner wall provides a transparent window to the vessel, its outer rim wall may be used to anchor and position a sensor in the rim, a temperature sensor may be inserted into a well in the inner rim wall, there is insulation of the gap between the rims, leads from a probe to the outer rim wall are secured in the wall, (Additionally, for full penetrations through the rim and vessel inner wall, such as for insertion of ports and conduits across the rim into the vessel, the double wall provides a convenient means to secure and seal such inserts in the rim body.
A disposable stir tank bioreactor vessel of any of the above claims wherein, in the double rim referred to in any of the above claims, the double rim comprises an opening or port allowing full penetration of ports, conduits or sensors across and through the rim and vessel inner wall.
A disposable stir tank bioreactor vessel of any of the above claims, wherein in the double rim referred to in any of the above claims, luer type fittings are used to secure probes, conduits or sensors.
A bioreactor vessel of any of the above claims, wherein an ISFET pH sensor or other ISFET sensor is embedded in the bioreactor vessel wall, its sensor tip positioned to contact fluid in the vessel.
A disposable stir tank bioreactor vessel of any of the above claims, said vessel comprising or attached to a reference electrode.
A disposable stir tank bioreactor vessel of any of the above claims, wherein the rim comprises a male luer lock fitted with an oxygen sensing probe or other sensing probe and further comprises a female luer lock adapter.
A disposable stir tank bioreactor system of any of the above claims wherein the system further comprises a manifold that is an array with multiple pump banks or receptacles for pumps.
A disposable stir tank method of using a bioreactor vessel, system or array wherein said method comprises the use of a bioreactor vessel, system or array of any of the above claims to grow a culture of biological cells.
A disposable stir tank bioreactor vessel such that inside said vessel there is a rotatable shaft, said shaft comprising a plurality (two or more) concentric tubes such that there is a space between each tube and its closest neighboring tube, such that said space is accessible by bioreactor fluid from below (preferably the top of the space is not blocked thereby permitting continuous upward flow of fluid within the space).
A disposable stir tank disposable stir tank bioreactor vessel comprising internal vertical columns, said columns either solid with an external surface or tubular with both internal and external surfaces.
A bioreactor vessel, such that inside said vessel there is a rotatable shaft, said vessel further comprising one or more platforms (for example discs) centered around and connected to said shaft, said vessel further comprising a three-dimensional structure attached to said platform, said structure coated at least in part with a material permitting cell attachment and growth (preferably adapted for animal or human cells).
A disposable stir tank bioreactor vessel, such that inside said vessel there is a rotatable shaft, said vessel further comprising a screened enclosing a space (or volume of fluid) are surrounding the shaft so as to not permit microcarriers that are in that space of volume from escaping that space or volume.
A method of preparing a sterile bioreactor vessel or bioreactor system said method comprising separately sterilizing two components of said bioreactor vessel or system and then combining them in a sterile room under sterile conditions.
A method of claims 60, 61, 62, 63, or 64 wherein one component is a probe or sensor that comprises an enzyme. 64, A bioreactor controller comprising
- a controller housing,
- a vessel receptacle upon which a bioreactor vessel can be placed, said vessel receptacle part of or attached to a heating block, and/or
- one or two pump manifolds, each manifold comprising a plurality (one or more) of pump banks (a/k/a receptacles) upon which a peristaltic pump is placed, each pump comprising a motor with a rotatable shaft, a pump base and a pump head, said base comprising a surface with a groove, said head comprising rollers, said groove and rollers for engaging tubing and driving fluid through the tube by a peristaltic displacement mechanism,
- wherein each pump manifold is vertically disposed along on a corner of the controller housing, said corner along the edge of a front surface of the controller housing such that said front surface faces a bioreactor vessel placed on the vessel receptacle,
- wherein the motor shaft axis is at angle greater than zero (preferably about 20 to 45 degrees) away from the front surface so that it will not point at a bioreactor vessel on the vessel receptacle.
A disposable stir tank bioreactor vessel of any of the foregoing claims wherein other than the stirrer shaft and impeller there are no probes, sensors or other inserts protruding into the interior of the vessel.
A disposable stir tank bioreactor system of any of the foregoing claims wherein other than the stirrer shaft and impeller there are no probes, sensors or other inserts protruding into the interior of the vessel.
Dependencies are inferred from the claim text.